200914035 九、發明說明: 相關申請案之交互參考案 本申請案主張2007年9月5日申請之美國臨時專利申 請案第60/967,510號之利益,其內容完整以參考文獻倂入本 文。 【發明所屬之技術領域】 本發明一般而言係關於傷口癒合,更具體而言,係關於 使用沸石系止血裝置促進傷口癒合之方法。 【先前技術】 血液是一種液體組織,包括分散於液相之紅血球、白血 球、小體(c 〇 r p u s c 1 e s )、及血小板。液相爲血榮,血漿包括 酸、脂質、溶解之電解質及蛋白質。蛋白質懸浮於液相,可 藉多種方法中之任一者諸如過濾、離心、電泳及免疫化學技 術,而由液相中分離。一種懸浮於液相之特殊蛋白質爲纖維 蛋白原(fibrinogen)。當發生出血時,纖維蛋白原與水及凝 血酶(thrombin )(—種酵素)反應形成纖維蛋白,其不溶 於血液並聚合形成血凝塊。 於多種情形’動物包括人類可能受傷。通常此等傷口會 造成出血。於某些情形,傷口與出血輕微,除了簡單的急救 之外只需要正常凝血功能。然不幸地於其它情形,可能發生 大出血。此種大出血情況通常需要特殊裝置及設備以及受訓 人員施予適當輔助。若不能立即取得此等輔助,則可能出現 血液過度喪失。當出血嚴重時’有時即刻取得設備及受訓人 員,其仍不足以即時停止血液流出。 200914035 一旦停止出血,可開始傷口癒合過程。此過程爲身體修 復皮膚或表皮損傷之初始機制。此過程被分成三階段’即’ (1)炎症期;(2)增生期;及(3)重塑期。此等階段主要 爲連續,但其於某時期可能於某程度重疊。炎症期典型範圍 由受傷當時至2-5日;增生期典型範圍由約2日至約3週; 重塑期典型範圍爲由約3週至約2年。炎症期中之活動包括 止血;細菌、剝落物及受損組織之吞噬作用(phagocytosis ); 及血液凝固因子之釋放(例如,因子VIII、因子IX、及因 子XI ),此血液凝固因子會使血小板凝聚因而誘導增生期。 增生期中之活動包括新血管之生長、膠原蛋白沉積、新組織 形成、及傷口收縮。於重塑期,上皮細胞越過傷口生長而形 成被覆物。 當剩下傷口自行癒合時,傷口傾向透過此三階段以緩慢 步伐及根據數因子進行。此等因子包括血液的特定構成、受 傷者之年齡、及與受傷組織有關之特定細節諸如水合程度、 傷口位置、獲得傷口的態樣、受傷者之營養攝取等。經常地, 無介入促進及加速癒合過程而使傷口癒合時可能造成增加 疼痛之感染及使受傷者不舒服,及/或延長不欲之藥物治療。 S於前述,所需者爲一種加速癒合過程以減少其欲效果 之方法。 【發明內容】 發明摘述 於一態樣中,本發明係關於一種降低傷口癒合所需時間 之方 '法。於此方法,塗敷有效量之止血劑至傷口。如此進行 200914035 時’增加傷口周圍組織之炎症以促進纖維母細胞沉積,因而 加速隨後之傷口收縮並啓動增生癒合階段。然後組織之再上 皮化可以較未塗敷止血劑於傷口之更快速度發生。 於另一態樣中,本發明係關於一種促進出血傷口癒合之 方法。於此方法中,將止血劑塗布於基質上,接著將其敷於 出血傷口因而塗敷有效量之止血劑於此傷口。如此進行時, 會刺激於傷口上、傷口內、傷口周圍或傷口附近之組織,將 纖維母細胞沉積於傷口組織。然後此組織會以較未塗敷止血 劑之更快速度再上皮化。 於另一態樣中,本發明係關於一種加速出血傷口癒合之 方法。於此方法,塗敷止血劑至出血傷口以促進癒合過程。 如此進行時,於出血傷口中之凝血串級及血小板凝集被加 速,並降低自傷口的出血,因而造成於出血傷口之組織局部 炎症及隨後組織之收縮。炎症及收縮造成纖維母細胞沉積之 增加。此過程之利用提供於癒合出血所需時間之增加,當與 未施予止血劑於出血傷口相比較時。 本發明之一優點爲較未以止血劑治療之傷口其傷口癒 合更快。尤其,纖維母細胞於傷口位置沉積之增加會加速癒 合過程。 本發明之另一優點爲降低與傷口癒合有關之風險,即, 會降低延遲癒合過程的感染之發作。因來自傷口之血液較未 使用止血劑更快凝固,凝結物栓塞更快形成於傷口上以形成 一抗細菌障壁。 【實施方式】 200914035 較佳具體實施例之詳細說明 本文所掲示者係經由改善傷口癒合初始階段之情況及 加速隨後傷口癒合階段’而降低於急性或慢性傷害後之傷口 癒合時間之方法。此等方法典型運用以有效量塗敷於出血傷 口以促進止血之組成物。此等組成物一般包含作爲活性成分 之止血劑,其可經由吸收至少一部分血液之液相因而促進凝 固以最小化或停止血液流出。 於本發明之一具體實施例,此止血劑爲沸石或其他分子 篩物質。本發明並未限於此,然而,其他物質亦爲本發明之 範疇。如本文之使用,“沸石”一詞係指具有無需使結晶結構 顯著改變而被脫水的能力之鋁矽酸鹽結晶形式。此沸石可包 括一種或多種離子諸如鈣部分及鈉部分。沸石之較佳分子 結構爲“ A型”晶體,即,具有界限圓形開口或實質上圓形開 口之立方結晶結構之晶體。 此沸石可與具有脫水能力而不會造成結晶結構顯著變 化之其它材料混合或以其它方式結合。此等材料包括(但未 限於)硫酸鎂、偏磷酸鈉、氯化鈣、糊精、前述材料之組合、 及前述材料之水合物。 使用於所揭示應用之沸石可爲天然產生或合成產生。 發現許多種天然沸石於澱積環境下以及於其它位置呈沈積 物。可應用於本文所述組成物之天然沸石包括(但不限於)方 沸石(analcite)、菱沸石(chabazite)、片沸石(heulandite)、鈉 沸石(natrolite)、銻沸石(stilbite)、及湯姆沸石(thomosonite)。 亦可於本文所述組成物及方法中使用之合成沸石通常係經 200914035 由其中稀土氧化物經以矽酸鹽取代,鋁氧、或鋁氧與鹼金屬 氧化物或鹼土金屬氧化物之組合取代之方法製造。 可與各種材料或其他止血劑一起與沸石被施予至傷 口’經由混合、結合、或倂入沸石中以維持傷口部位之無菌 環境’或提供可補充沸石凝血功能之功能。可使用之示例材 料包括(但不限於)醫藥活性組成物諸如抗生素、抗真菌劑、 抗細菌劑、抗微生物劑、抗炎劑、止痛劑、抗組織胺(例如, 希美提定(cimetidine)、克洛菲尼拉明(chloropheniramine)順 丁烯二酸鹽、待芬海卓明(diphenhydramine)鹽酸鹽、及波美 雜今(promethazine)鹽酸鹽)、碘、含有銀離子之化合物等。 尤其抗細菌成分經降低細菌於傷口之增生而促進癒合過 程。可被倂入而提供額外止血功能之其它材料包括抗壞血 酸、凝血酸(tranexamic acid)、芸香音(rutin)及凝血酶 (thrombin )。亦可添加對傷口部位具有期望功效之本草藥 劑。 可應用沸石或止血劑於惰性基質或媒劑而被施予於出 血傷口。於應用於如此惰性基質或媒劑上,沸石或其他止血 劑較佳爲粉末形式。沸石之粉末形式可以任何適當操作獲 得。例如,粉末化沸石可經粉碎、擠壓、輾壓、或磨成粉狀 粗糙沸石材料。然而本發明並未限於此,可運用將沸石有技 巧地使用成爲與本發明有關技藝中彼等熟習此項技藝者已 知粉末形式之其他方法。 於本發明之其他具體實施例,塗覆於基質上之止血劑爲 一種生物活性玻璃。如本文之使用,“生物活性玻璃”一詞係 200914035 指表面-活性玻璃狀陶瓷材料,其爲與人類組織爲生物可相 容之材料。生物活性玻璃之組成物促進於水性環境中之快速 離子交換。生物活性玻璃可以配方群集之任何一種被定義, 但其主要爲氧化物之混合物。一般而言,生物活性玻璃包括 二氧化矽及氧化鈣。可倂入生物活性玻璃之其他材料包括 (但不限於)氧化鈉及五氧化碟。另可被加入生物活性玻璃 之其他材料包括(但不限於)上述醫藥活性組成物。 於其他具體實施例,塗覆於基質之材料可爲含砂氧化 物、各種含矽氧化物之混合物、任何型式之中孔材料、黏土 (例如’綠坡縷石(attapulgite )、膨潤土、高嶺土、或其組 合)、矽藻土、具止血特性之生物組成物(例如,殼聚糖、 凝血酶、纖維蛋白、因子VII或類似酵素、或其組成物)、 或任何其他具有止血特性之組成物。此等材料可與沸石或其 他分子篩合倂使用。 僅管本文所述組成物及其製造方法引述活性成分爲沸 石’彼等熟習該項技術者應了解此止血劑及其製造方法可另 外倂入生物活性玻璃、含砂氧化物、中孔材料、黏土、砂藻 土、生物組成物、或其任何組合以界定此活性成分。 於調配止血劑上’將沸石黏附於基質。沸石及基皙材料 之間的黏附機制可爲庫倫力、分隔結合材料、或額外止血 劑。於具體實施例中使用分隔結合材料,此材料可爲具有充 分使組成物保留於基質以留住活性成分的性質之任何生物 可相容組成物。 現參照第1圖’止血劑一般顯示於10。於—示例具體實 200914035 施例,止血劑10包含沸石’示於12,設置於基質14之上。 基質1 4可爲黏土、人工或經加工凝膠或膠化劑,或一些其 他型式之材料諸如結合沸石1 2於其上之塑膠或其他支持沸 石者。亦可使用另外的黏著劑黏著沸石12至基質14。 沸石系止血劑促進止血’接著加速凝血串級及血小板凝 聚之進行。此等劑亦經由改善傷口癒合之炎症階段使其更快 開始增生期而促進急性及慢性(包括缺血)傷害後之傷口癒 合。因此此劑減少血液流失及相關倂發症風險諸如降低可能 延遲傷口癒合之感染。此外’此劑造成增加纖維母細胞沉積 及傷口收縮之局部炎症。 此劑於傷口癒合之另一應用涉及清創,其爲自傷口以手 術或機械移除感染組織。此程序有時用於慢性傷口以促進健 康組織之修復,但已知於組織移除結果上會引起顯著出血。 此劑可作爲停止出血之用及經直接接觸殺菌(若使用此裝置 之抗菌劑形式)。 實施例-傷口癒合速率之比較 ϋ 於一硏究中,使用沸石系止血劑治療於豬受試者身上創 造的深部局部深傷口。將止血劑置於使血流通過接觸此止血 劑之囊袋中。以三種方式之一種將此囊袋敷於每一豬受試 者。第一種,將此囊袋敷於傷口 3分鐘,然後以紗布覆蓋傷 口。第二種,將此囊袋敷於傷口 24小時每日並以紗布覆蓋。 於第二種方式中,每24小時期間後更換止血劑及囊袋。第 三種,於豬受試者製造傷口且不處理。4日後,評估傷口之 上皮化並比較。以沸石系止血劑處理之傷口具有較未處理傷 -11- 200914035 口更高速率之上皮化。 參照第2圖,於傷口癒合速率之比較,當每日敷止血劑 3分鐘其較當敷止血劑24小時期間者可見再上皮化過程以 更快速率進行,而敷止血劑2 4小時期間者與未處理者比較 爲更快。尤其’當每日施予止血劑3分鐘之情形中,如長條 圖2 0所示,指出約5日後再上皮化(約1 〇 % ),而未處理傷 口(長條圖24 )及施予止血劑於傷口上24小時期間(長條 圖26 ),第一次注意到再上皮化於約6日後。注意到於兩止 ί 血劑處理傷口約7日後完成再上皮化,而於約7日後未處理 傷口仍僅有約50 %再上皮化。 僅管已經就詳細具體實施例顯示及描述本發明,但彼等 熟習此項技藝者可了解其可作多項變化,且可未悖離本發明 之範圍以相當元件來取代其元件。此外,可未悖離其主要範 圍做出修改來讓特定情況或材料配合本發明之教示。因此, 預期本發明非僅限於前文詳細說明揭示之具體實施例,而是 本發明涵蓋全部落入於隨附之申請專利範圍之具體實施例。 、 【圖式簡單說明】 第1圖爲止血劑粒子之橫切面視圖;及 第2圖爲顯示未處理傷口及以止血劑處理傷口之再上皮 化速率之圖形陳述。 【主要元件符號說明】 10 止血劑 12 沸石 14 基質 -12- 200914035 20 每日施予止血劑3分鐘 2 4 未處理傷口 26 施予止血劑2 4小時 13。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 TECHNICAL FIELD OF THE INVENTION The present invention relates generally to wound healing and, more particularly, to a method for promoting wound healing using a zeolite-based hemostasis device. [Prior Art] Blood is a liquid tissue including red blood cells, white blood cells, small bodies (c 〇 r p u s c 1 e s ), and platelets dispersed in a liquid phase. The liquid phase is blood, and the plasma includes acids, lipids, dissolved electrolytes and proteins. The protein is suspended in the liquid phase and can be separated from the liquid phase by any of a variety of methods such as filtration, centrifugation, electrophoresis, and immunochemical techniques. A special protein suspended in the liquid phase is fibrinogen. When bleeding occurs, fibrinogen reacts with water and thrombin (-enzyme) to form fibrin, which is insoluble in the blood and polymerizes to form a blood clot. In many cases, animals, including humans, may be injured. Usually these wounds can cause bleeding. In some cases, the wound and bleeding are mild, requiring only normal coagulation in addition to simple first aid. Unfortunately, in other situations, major bleeding may occur. Such major bleeding conditions usually require special equipment and equipment as well as appropriate assistance from the trainee. If these aids are not available immediately, excessive blood loss may occur. When the bleeding is severe, the equipment and trainees are sometimes obtained immediately, which is still not enough to stop the blood flow immediately. 200914035 Once the bleeding stops, the wound healing process can begin. This process is the initial mechanism by which the body repairs skin or epidermal damage. This process is divided into three stages 'i.e.' (1) inflammatory phase; (2) proliferative phase; and (3) remodeling phase. These stages are mainly continuous, but they may overlap to some extent during a certain period. The inflammatory phase typically ranges from the time of injury to 2-5 days; the proliferative phase typically ranges from about 2 days to about 3 weeks; and the remodeling period typically ranges from about 3 weeks to about 2 years. Activities during the inflammatory phase include hemostasis; phagocytosis of bacteria, exfoliated and damaged tissues; and release of blood coagulation factors (eg, factor VIII, factor IX, and factor XI), which coagulates platelets Thus the proliferative phase is induced. Activities in the proliferative phase include growth of new blood vessels, collagen deposition, new tissue formation, and wound contraction. During the remodeling period, epithelial cells grow over the wound to form a coating. When the remaining wound heals itself, the wound tends to progress through these three stages at a slow pace and according to a number factor. These factors include the specific composition of the blood, the age of the victim, and the specific details associated with the injured tissue such as the degree of hydration, the location of the wound, the condition in which the wound is obtained, the nutritional intake of the injured person, and the like. Frequently, no intervention promotes and accelerates the healing process, which may result in increased pain infection and discomfort to the wounded, and/or prolonged undesired medication. In the foregoing, it is desirable to have a method of accelerating the healing process to reduce its desired effect. SUMMARY OF THE INVENTION In one aspect, the present invention is directed to a method of reducing the time required for wound healing. In this method, an effective amount of a hemostatic agent is applied to the wound. By doing so at 200914035, the inflammation of the tissue surrounding the wound is increased to promote fibroblast deposition, thereby accelerating subsequent wound contraction and initiating a proliferative healing phase. The re-epithelialization of the tissue can then occur at a faster rate than the uncoated hemostatic agent at the wound. In another aspect, the invention is directed to a method of promoting healing of a bleeding wound. In this method, a hemostatic agent is applied to a substrate which is then applied to a bleeding wound and an effective amount of a hemostatic agent is applied to the wound. When so, it stimulates tissue on the wound, in the wound, around the wound, or near the wound, depositing fibroblasts into the wound tissue. This tissue will then re-epithelialize at a faster rate than the uncoated hemostatic agent. In another aspect, the invention is directed to a method of accelerating healing of a bleeding wound. In this method, a hemostatic agent is applied to the bleeding wound to promote the healing process. In doing so, coagulation cascades and platelet aggregation in the bleeding wound are accelerated and bleeding from the wound is reduced, resulting in localized inflammation of the tissue in the bleeding wound and subsequent contraction of the tissue. Inflammation and contraction cause an increase in fibroblast deposition. The use of this procedure provides an increase in the time required to heal bleeding when compared to when no hemostatic agent is administered to the bleeding wound. One advantage of the present invention is that the wounds are healed faster than wounds that are not treated with a hemostatic agent. In particular, an increase in the deposition of fibroblasts at the wound site accelerates the healing process. Another advantage of the present invention is to reduce the risk associated with wound healing, i.e., to reduce the onset of infection that delays the healing process. Since the blood from the wound solidifies faster than without the hemostatic agent, the clotting of the condensate forms faster on the wound to form an anti-bacterial barrier. [Embodiment] 200914035 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The present invention is directed to a method of reducing the healing time of wounds after acute or chronic injury by improving the initial stage of wound healing and accelerating the subsequent stage of wound healing. These methods typically employ a composition that is applied to the bleeding wound in an effective amount to promote hemostasis. Such compositions generally comprise a hemostatic agent as an active ingredient which promotes coagulation by absorbing at least a portion of the blood phase of the blood to minimize or stop blood efflux. In one embodiment of the invention, the hemostatic agent is a zeolite or other molecular sieve material. The present invention is not limited thereto, however, other substances are also within the scope of the invention. As used herein, the term "zeolite" refers to a crystalline form of aluminosilicate having the ability to be dehydrated without significant changes in the crystalline structure. The zeolite may comprise one or more ions such as a calcium moiety and a sodium moiety. The preferred molecular structure of the zeolite is a "type A" crystal, i.e., a crystal having a cubic circular opening or a substantially circular open cubic crystal structure. This zeolite can be mixed or otherwise combined with other materials which have the ability to dehydrate without causing significant changes in the crystalline structure. Such materials include, but are not limited to, magnesium sulfate, sodium metaphosphate, calcium chloride, dextrin, combinations of the foregoing, and hydrates of the foregoing. Zeolites useful in the disclosed applications can be produced naturally or synthetically. Many natural zeolites have been found to deposit in the deposition environment as well as at other locations. Natural zeolites useful in the compositions described herein include, but are not limited to, analcite, chabazite, heulandite, natrolite, stilbite, and tom zeolite. (thomosonite). Synthetic zeolites which may also be used in the compositions and methods described herein are typically replaced by a combination of a rare earth oxide with a phthalate, an aluminum oxide, or a combination of an aluminum oxide and an alkali metal oxide or an alkaline earth metal oxide, in 200914035. The method of manufacture. The zeolite can be administered with the various materials or other hemostatic agents to the wound 'by mixing, binding, or incorporation into the zeolite to maintain the sterile environment of the wound site' or to provide a function to supplement the coagulation function of the zeolite. Exemplary materials that may be used include, but are not limited to, pharmaceutically active compositions such as antibiotics, antifungals, antibacterials, antimicrobials, anti-inflammatory agents, analgesics, antihistamines (eg, cimetidine, Chloropheniramine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride, iodine, a compound containing silver ions, and the like. In particular, antibacterial ingredients promote the healing process by reducing the proliferation of bacteria in the wound. Other materials that can be invaded to provide additional hemostasis include ascorbic acid, tranexamic acid, rutin, and thrombin. It is also possible to add a herbal preparation that has the desired effect on the wound site. The zeolite or hemostatic agent can be applied to the bleeding wound in an inert matrix or vehicle. For use on such inert substrates or vehicles, the zeolite or other hemostatic agent is preferably in powder form. The powder form of the zeolite can be obtained by any suitable operation. For example, the powdered zeolite can be comminuted, extruded, pulverized, or ground into a powdery coarse zeolitic material. However, the invention is not limited thereto, and other methods of using the zeolite in a powder form which is well known to those skilled in the art can be utilized. In other embodiments of the invention, the hemostatic agent applied to the substrate is a bioactive glass. As used herein, the term "bioactive glass" refers to a surface-active glassy ceramic material that is biocompatible with human tissue. The composition of the bioactive glass promotes rapid ion exchange in an aqueous environment. Bioactive glass can be defined as any of the formula clusters, but it is primarily a mixture of oxides. In general, bioactive glasses include ceria and calcium oxide. Other materials that can be incorporated into bioactive glass include, but are not limited to, sodium oxide and pentoxide disks. Other materials which may be added to the bioactive glass include, but are not limited to, the above pharmaceutically active compositions. In other embodiments, the material applied to the substrate may be a sand-containing oxide, a mixture of various cerium-containing oxides, any type of mesoporous material, clay (eg, 'attapulgite, bentonite, kaolin, Or a combination thereof, a diatomaceous earth, a biological composition having hemostatic properties (for example, chitosan, thrombin, fibrin, factor VII or a similar enzyme, or a composition thereof), or any other composition having hemostatic properties . These materials can be used in combination with zeolite or other molecular sieves. The compositions described herein and the methods for their manufacture recite the active ingredients as zeolites. Those skilled in the art should understand that the hemostatic agents and methods for their manufacture may additionally incorporate bioactive glass, sand oxides, mesoporous materials, Clay, diatomaceous earth, biological composition, or any combination thereof to define the active ingredient. The zeolite is adhered to the matrix on the formulation of the hemostatic agent. The adhesion mechanism between the zeolite and the base material can be Coulomb force, separate binding materials, or additional hemostatic agents. A separate bonding material is used in a particular embodiment, and the material can be any biocompatible composition having the property of retaining the composition in the matrix to retain the active ingredient. Referring now to Figure 1, the hemostatic agent is generally shown at 10. In the example embodiment 200914035, the hemostatic agent 10 comprises zeolite 'shown at 12 and disposed over the substrate 14. The matrix 14 can be a clay, an artificial or processed gel or gelling agent, or some other type of material such as a plastic or other supporting zeolite that incorporates the zeolite 12. Zeolite 12 can also be adhered to matrix 14 using an additional adhesive. The zeolite-based hemostatic agent promotes hemostasis' followed by accelerated coagulation cascade and platelet aggregation. These agents also promote wound healing after acute and chronic (including ischemia) injury by improving the inflammatory phase of wound healing to initiate a proliferative phase more quickly. This agent therefore reduces blood loss and associated risk of complications such as reducing infections that may delay wound healing. In addition, this agent causes local inflammation that increases fibroblast deposition and wound contraction. Another application of this agent to wound healing involves debridement, which involves surgically or mechanically removing infected tissue from the wound. This procedure is sometimes used for chronic wounds to promote repair of healthy tissue, but is known to cause significant bleeding on tissue removal results. This agent can be used as a stop bleeding and direct contact sterilization (if an antibacterial agent is used in this device). EXAMPLES - Comparison of wound healing rates 沸石 In one study, a zeolite-based hemostatic agent was used to treat deep local deep wounds created in pig subjects. The hemostatic agent is placed in a pocket that allows blood to flow through the hemostatic agent. This pouch was applied to each pig subject in one of three ways. First, the pouch was applied to the wound for 3 minutes and the wound was covered with gauze. Second, the pouch was applied to the wound for 24 hours daily and covered with gauze. In the second mode, the hemostatic agent and pouch are replaced after every 24 hours. Third, wounds are made in pig subjects and are not treated. After 4 days, the epithelialization of the wound was evaluated and compared. Wounds treated with a zeolite-based hemostatic agent had a higher rate of epithelialization than the untreated injury -11-200914035. Referring to Fig. 2, in the comparison of wound healing rate, when the hemostatic agent is applied daily for 3 minutes, it can be seen that the re-epithelialization process is performed at a faster rate during the 24-hour period when the hemostatic agent is applied, and the hemostatic agent is administered for 24 hours. It is faster than unprocessed. In particular, when the hemostatic agent is administered daily for 3 minutes, as shown in the bar graph 20, it is indicated that the epithelialization (about 1%) is performed after about 5 days, while the untreated wound (bar Figure 24) and The hemostatic agent was administered to the wound for 24 hours (bar graph 26), and the first time it was noted that re-epithelialization was about 6 days later. It was noted that re-epithelialization was completed approximately 7 days after the wound treatment of the blood, and only about 50% of the untreated wounds after about 7 days were re-epithelialized. The present invention has been shown and described with respect to the specific embodiments thereof, and it is understood by those skilled in the art that various changes can be made without departing from the scope of the invention. In addition, modifications may be made to adapt a particular situation or material to the teachings of the invention. Therefore, the present invention is intended to be limited to the specific embodiments disclosed herein. [Simplified Schematic Description] Fig. 1 is a cross-sectional view of the blood agent particles; and Fig. 2 is a graphical representation showing the rate of re-epithelialization of the untreated wound and the wound treated with the hemostatic agent. [Main component symbol description] 10 Hemostatic agent 12 Zeolite 14 Matrix -12- 200914035 20 Daily administration of hemostatic agent for 3 minutes 2 4 Untreated wound 26 Administration of hemostatic agent 2 4 hours 13